Incidence and correlated factors of beta cell failure in a 4-year follow-up of patients with type 2 diabetes: a longitudinal analysis of the BETADECLINE study

Type 2 diabetes is associated with progressive deterioration of beta cell function and loss of glycemic control, with increased morbidity and mortality from microvascular and macrovascular complications. Factors predictive of beta cell decline are needed.

We have conducted a prospective evaluation of baseline predictors of beta cell dysfunction and insulin initiation in a cohort of outpatients with type 2 diabetes receiving stable treatment with oral hypoglycemic agents or dietary intervention, over a 4-year follow-up period.

Of 507 patients enrolled, 56 (10.8 %) experienced the study endpoint of initiation of insulin therapy. Univariate and multivariate Cox proportional hazard regression analyses revealed that the likelihood of initiating insulin therapy during follow-up increased with longer diabetes duration and with higher baseline values for hemoglobin A1c, fasting plasma glucose, triglycerides, proinsulin, interleukin-6, Homeostatic Model Assessment-IR and lower values for Homeostatic Model Assessment-B. The likelihood of initiating insulin therapy increased by 46 % for each 1 % increase (10.9 mmol/mol) in baseline hemoglobin A1c and by 6 % for each unit increase (1 ng/l) in baseline IL-6 level. The risk was fourfold higher in the lowest versus highest Homeostatic Model Assessment-B quartile. Treatment with metformin plus a secretagogue increased the risk by fourfold.

Our results show that commonly measured parameters may predict treatment failure in type 2 diabetes and suggest that early treatment with metformin plus secretagogues may foretell this failure.